1. Field of the Invention
The present invention relates to the local administration of therapeutic agents and/or therapeutic agent combinations for the prevention and treatment of vascular disease, and more particularly to intraluminal medical devices having reservoirs with retention features for the local delivery of therapeutic agents and/or therapeutic agent combinations.
2. Discussion of the Related Art
Many individuals suffer from circulatory disease caused by a progressive blockage or narrowing of the blood vessels that perfuse the heart and other major organs. More severe blockage of blood vessels in such individuals often leads to hypertension, ischemic injury, stroke, or myocardial infarction. Atherosclerotic lesions, which limit or obstruct coronary blood flow, are the major cause of ischemic heart disease. Alternately, spontaneous rupture of inflammatory atherosclerotic lesions or vulnerable plaque may lead to intermittent or complete thrombotic occlusion of an artery causing ischemic injury such as stroke and/or acute myocardial infarction. Percutaneous transluminal coronary angioplasty is a medical procedure whose purpose is to increase blood flow through an artery. Percutaneous transluminal coronary angioplasty is the predominant treatment for coronary vessel stenosis. The increasing use of this procedure is attributable to its relatively high success rate and its minimal invasiveness compared with coronary bypass surgery. A limitation associated with percutaneous transluminal coronary angioplasty is the abrupt closure of the vessel, which may occur immediately after the procedure and restenosis, which occurs gradually following the procedure. Additionally, restenosis is a chronic problem in patients who have undergone saphenous vein bypass grafting. The mechanism of acute occlusion appears to involve several factors and may result from vascular recoil with resultant closure of the artery and/or deposition of blood platelets and fibrin along the damaged length of the newly opened blood vessel.
Restenosis after percutaneous transluminal coronary angioplasty is a more gradual process initiated by vascular injury. Multiple processes, including thrombosis, inflammation, growth factor and cytokine release, cell proliferation, cell migration and extracellular matrix synthesis each contribute to the restenotic process.
Unlike systemic pharmacologic therapy, stents have proven useful in significantly reducing restenosis. Typically, stents are balloon-expandable slotted metal tubes (usually, but not limited to, stainless steel), which, when expanded within the lumen of an angioplastied coronary artery, provide structural support through rigid scaffolding to the arterial wall. This support is helpful in maintaining vessel lumen patency. In two randomized clinical trials, stents increased angiographic success after percutaneous transluminal coronary angioplasty, by increasing minimal lumen diameter and reducing, but not eliminating, the incidence of restenosis at six months (Serruys et al., 1994; Fischman et al., 1994). In addition, stents have become the treatment of choice for revascularization of a thrombosed coronary artery (acute myocardial infarction) in which rapid restoration of blood flow to ischemic myocardial tissue is the primary determinant of long term clinical benefit. Full restoration of coronary blood flow with a stent within 6 hours of presentation of symptoms, and preferably under 3 hour, has been shown to produce superior clinical outcomes over administration of a thrombolytic agent (tPA, streptokinase, etc.) to dissolve a thrombotic occlusion.
Stents utilized for the local delivery of rapamycins, including sirolimus, everolimus and other rapamycin analogs and derivatives (mTOR inhibitors), have proved more successful in significantly reducing restenosis and related complications following percutaneous transluminal angioplasty and other similar arterial/venous procedures than bare metal stents. Rapamycins may be incorporated onto or affixed to the stent in a number of ways. For example, the rapamycins may be incorporated into a polymeric matrix and then affixed to the surface of the stent by any suitable means. The rapamycins elute from the polymeric matrix over a given period of time and into the surrounding tissue.
Additionally, heparin coating of stents appears to have the added benefit of producing a reduction in sub-acute thrombosis after stent implantation. Thus, sustained mechanical expansion of a stenosed coronary artery with a stent has been shown to provide some measure of restenosis prevention, and the coating of stents with rapamycins and heparin has demonstrated both the feasibility and the clinical usefulness of delivering drugs locally, at the site of injured tissue.
Drug elution achieved by coated stents has been a recent development in this field. However, further development in stent technology has resulted in stents comprising drug eluting reservoirs. Stents with drug eluting reservoirs have enabled more flexibility and options in drug choice, deliverability, and treatments. With reservoir based drug eluting stents the drug component is typically located within the reservoir, which is in contrast to coated stents where the drug and polymer are formulated into a coating which is applied to portions of the stent surface. As stent designs continue to be refined and are made smaller and more flexible, and the service conditions for which these stents are utilized becomes more demanding, securement of the drug component within the reservoir will become more important and more difficult to reliably achieve. In addition to mechanical forces which may be imparted to the reservoir during delivery of the stent, the act of stent crimping and expansion may result in additional mechanical loading to the inlays within the reservoir of the stent.
Accordingly, there exists a need for a reservoir based drug eluting stent having improved reservoir features for the securement of the drugs or other therapeutic agents therein thereby enabling the drug inlay to remain unaffected during manufacture, preparation, delivery and available for the prevention and treatment of vascular injury as described above.